Urothelium: Difference between revisions

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The '''urothelium''' lines the upper portion of the genitourinary tract... and a bit of the lower part.
The '''urothelium''' lines the upper portion of the genitourinary tract, i.e. [[ureter]]s, [[urinary bladder]]), and a bit of the lower part.


=Normal histology=
=Normal urothelium=
===Gross===
====Extent of urothelium====
*[[Ureters]].
*Renal pelvis.
*[[Urinary bladder]].
*Part of the urethra.
=====Urethra in males=====
{{Main|Urethra}}
*Pre-prostatic urethra - transitional epithelium.
*[[Prostate gland|Prostatic]] urethra - transitional epithelium.
**Cancer arising at this site is ''[[prostatic urothelial carcinoma]]''.
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostratified columnar epithelium.
*Spongy urethra - pseudostratified columnar epithelium (proximal) & stratified squamous (distal).
 
===Microscopic===
Features:
*Maturation (cuboidal at base - squamoid at surface).
*Maturation (cuboidal at base - squamoid at surface).
**Surface cells called 'umbrella cells' (umbrella cells CK20+).
**Surface cells called 'umbrella cells' (umbrella cells CK20 +ve).
*Urothelium should be 4-5 cell layers thick.
*Urothelium should be 4-5 cell layers thick.
*+/-Prominent nucleoli.
*+/-Prominent [[nucleoli]].


*Should NOT have papillary architecture -- if it does it is likely [[cancer]]!
Note:
*Should '''not''' have a papillary architecture -- if it does it is likely [[cancer]]!
**If it is 'papillary' -- it must have fibrovascular cores.
**If it is 'papillary' -- it must have fibrovascular cores.


==Extent of urothelium==
===IHC===
*Ureters.
*Rare superficial [[CK20]] staining.
*Renal pelvis.
 
*Bladder.
====Image====
*Part of the urethra.
<gallery>
Image: Benign urothelium - CK20 -- high mag.jpg | Benign urothelium - CK20 - high mag. (WC)
===Urethra in males===
</gallery>
*Pre-prostatic urethra - transistional epithelium.
 
*Prostatic urethra - transistional epithelium.
===Sign out===
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostrat. columnar epithelium.
<pre>
*Spony urethra - pseudostratified columnar epi. (proximal) & strat. squamous (distal).
URINARY BLADDER LESION, TRANSURETHRAL RESECTION:
- UROTHELIAL MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
====Micro====
The sections shows urothelium with underlying tissue.  The urothelium is 4-5 cells thick. Umbrella cells are present. Few mononuclear inflammatory cells are seen in the subepithelial tissue.
 
The urothelium has no nuclear hyperchromasia and no significant nuclear enlargement. Mitotic activity is not identified. No papillary structures are present.


=Approach=
=Approach=
Line 47: Line 73:
#* Normal is 4-5 cell layers.
#* Normal is 4-5 cell layers.
# Nests of glandular cells
# Nests of glandular cells
#* Consider ''cystitis cystica'', ''cystitis glandularis'', ''cystitis cystica et glandularis'', ''Brunn's nest'', ''inverted papilloma''.
#* Consider ''[[cystitis cystica]]'', ''[[cystitis glandularis]]'', ''cystitis cystica et glandularis'', ''[[von Brunn's nest]]'', ''[[inverted urothelial papilloma|inverted papilloma]]''.
# Inflammation?
# Inflammation?
#* Michaelis-Gutman bodies?
#* Michaelis-Gutman bodies?
Line 73: Line 99:
===Flat urothelial lesions===
===Flat urothelial lesions===
Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:<ref>{{Ref GUP|155-163}}</ref>
Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:<ref>{{Ref GUP|155-163}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
| ||'''Normal'''||'''Reactive atypia'''||'''Flat urothelial hyperplasia'''||'''Urothelial dysplasia'''||'''UCC in situ'''||'''Invasive UCC'''
! Diagnosis
! Nuclear enlargement<br>(X stromal lymphocyte)
! Nucleoli
! size var., shape
! Polarity
! Mitoses
! Thickness
! Inflammation
! Other
|-
|-
|Nuclear enlargement<br>(X stromal lymphocyte) ||none (2x) ||moderate, prominent (3x) ||none (2x) ||moderate (3x) ||'''signif. (4-5x)'''|| signif. (4-5X)
| '''Normal'''
| none (2x)
| small
| none, round
| matures to surface
| none/minimal
| 4-5 cells
| none
| -
|-
|-
|Nucleoli ||small ||prominent ||small ||small, some multiple ||+/-large ||+/-large
|'''Reactive atypia'''
| moderate, prominent (3x)
| prominent  
| none, round
| as normal
| some, none atypical
| as normal
| '''severe, acute or chronic'''
| -
|-
|-
|size var., shape ||none, round ||none, round ||none, round ||mod. variation, some irregularity ||marked, irregular ||marked, irregular
| '''Flat urothelial hyperplasia'''
| none (2x)
| small
| none, round
| as normal
| as normal
| '''increased'''
| usu. none
| -
|-
|-
|Polarity ||matures to surface ||as normal ||as normal ||'''lost''' ||lost ||lost
| '''[[Urothelial dysplasia]]'''
| moderate (3x)
| small, some multiple
| mod. variation, some irregularity
| '''lost'''
| rare, none atypical
| as normal
| usu. none
| -
|-
|-
|Mitoses ||none/minimal ||some, none atypical ||as normal ||rare, none atypical ||common, atypical ||common, atypical
| '''[[Urothelial carcinoma in situ]]'''
| '''signif. (4-5x)'''
| +/-large
| marked, irregular
| lost
| common, atypical
| thin, thick or norm.
| +/-
| -
|-
|-
|Thickness ||4-5 cells ||as normal ||'''increased''' ||as normal ||thin, thick or norm. ||thin, thick or norm.
| '''[[Urothelial carcinoma|Invasive UCC]]'''
|-
| signif. (4-5X)
|Inflammation ||none ||'''severe, acute or chronic''' ||usu. none ||usu. none ||+/- ||+/-
| +/-large
|-
| marked, irregular
|Other ||- ||- ||- ||- ||- ||'''stromal invasion'''
| lost
| common, atypical
| thin, thick or norm.
| +/-
| '''stromal invasion'''
|-
|-
|}
|}
Line 97: Line 175:
===Papillary urothelial lesions===
===Papillary urothelial lesions===
Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
| ||'''Papilloma''' ||'''PUNLMP''' ||'''low grade PUCC''' ||'''high grade PUCC'''
! Diagnosis
|-
! Papillae features
|papillae features ||'''fat papillae''', <br>'''thick FV core''' ||'''slender FV core''' ||slender FV core, <br>'''thick epithelium''' ||mixed population
! Papillae branching
|-
! Papillae fusion
|papillae branching ||rare ||uncommon ||frequent ||common
! Nuclear size
! Mitoses
! DDx
! IHC
! Other
! Key feature
|-
| [[Urothelial papilloma|Papilloma]]
| '''fat papillae''', <br>'''thick FV core'''
| rare
| none
| normal (2x lymphocyte)
| very rare basal
| [[PUNLMP]], low gr. PUCC
| p53-, CK20+ umbrella cells
| cytologically normal
| normal cells,<br>fat papillae
|-
|-
|papillae fusion ||none ||rare ||some ||common
| [[PUNLMP]]
| '''slender FV core'''
| uncommon
| rare
| '''enlarged - uniform'''
| rare basal only
| papilloma, low gr.
| CK20+ umbrella
| low cellular density (@ low power) vs. low gr.<ref>GAG. 26 February 2009.</ref>
| uniformly enlarged cell pop., <br>slender papillae
|-
|-
|nuclear size ||normal (2x lymphocyte) ||'''enlarged - uniform''' ||'''enlarged with variation''' ||'''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
| [[Low grade papillary urothelial carcinoma|Low grade PUCC]]
| slender FV core, <br>'''thick epithelium'''  
| frequent
| some
| '''enlarged with variation'''
| infreq., usually basal
| PUNLMP, high gr.
| -/+ p53, CK20+ umbrella
| +/- small nucleoli
| nuc. pleomorphism, <br> thick epithelium
|-
|-
|mitoses ||very rare basal || rare basal only ||infreq., usually basal ||common, everywhere
| [[High grade papillary urothelial carcinoma|High grade PUCC]]
|-
| mixed population
|DDx ||PUNLMP, low gr. PUCC ||papilloma, low gr. ||PUNLMP, high gr. ||low gr., invasive UCC
| common
|-
| common
|IHC ||p53-, CK20+ umbrella cells ||CK20+ umbrella ||-/+ p53, CK20+ umbrella ||'''diffuse CK20+''', p53+ in 50%
| '''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
|-
| common, everywhere
|Other ||cytologically normal ||low cellular density (@ low power) vs. low gr.<ref>GAG. 26 February 2009.</ref> ||+/- small nucleoli ||nucleoli prominent
| low gr., invasive UCC
|-
| '''diffuse CK20+''', p53+ in 50%
|Key feature ||normal cells,<br>fat papillae ||uniformly enlarged cell pop., <br>slender papillae ||nuc. pleomorphism, <br> thick epithelium ||marked nuclear pleomorphism
| nucleoli prominent
| marked nuclear pleomorphism
|-
|-
|}
|}
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=Flat urothelial lesions=
=Flat urothelial lesions=
==Overview==
==Overview==
Several different benign & pre-malignant diagnoses can be made:
Several different benign & pre-malignant diagnoses can be made.
*Reactive atypia.
 
The World Health Organization classification is:<ref name=pmid19762067>{{Cite journal  | last1 = Hodges | first1 = KB. | last2 = Lopez-Beltran | first2 = A. | last3 = Davidson | first3 = DD. | last4 = Montironi | first4 = R. | last5 = Cheng | first5 = L. | title = Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features. | journal = Hum Pathol | volume = 41 | issue = 2 | pages = 155-62 | month = Feb | year = 2010 | doi = 10.1016/j.humpath.2009.07.002 | PMID = 19762067 }}</ref>
*Reactive urothelial atypia.
*Flat urothelial hyperplasia.
*Flat urothelial hyperplasia.
*Urothelial dysplasia.
*Urothelial atypia of unknown significance.
*Urothelial carcinoma in situ.
*[[Urothelial dysplasia]] (low-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Invasive urothelial carcinoma.
*Invasive urothelial carcinoma.


==Urothelial carcinoma in situ==
==Mild urothelial atypia in normal urothelium==
===General===
*Lack papillae.
 
===Microscopic===
Features:
*Nuclear changes '''key feature'''.
**Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
***Normal urothelium approx. 2x the size of stromal lymphocytes.
**Nuclear pleomorphism - marked variation in size of nuclei.
*Disordered arrangement/crowding of cells.
**In normal urothelium the cell line-up on the basement membrane.
*Umbrella cells often absent.
*Mitoses present.
*+/-Enlarged nucleoli.
 
==Urothelial cell carcinoma==
:See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].
*Abbreviated ''UCC''.
*[[AKA]] ''urothelial carcinoma''.
 
===General===
===General===
*These lesions lack papillae and are typical flat.
*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and [[renal cell carcinoma]].  
*Uncommon.
*Considered to be [[normal urothelium]].


===Microscopic===
===Microscopic===
Features:
Features:<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Nuclear pleomorphism - '''key feature'''.
*Umbrella cells have:
**Compare nuclei to one another.
**Mild nuclear enlargement ~3-4x lymphocyte.
*Increased N/C ratio.
**Round/regular nuclear membranes.
*Lack of maturation to surface (important).
**+/-Multi-nucleation.
**Focally clear cytoplasm with cobwebs.
***Clear cytoplasm with eosinophilic reticulations.
*+/-Inflammation.
*No mitotic activity.


*Cells become dyscohesive.
DDx:<ref>URL: [http://pathology.jhu.edu/bladder/definitions.cfm http://pathology.jhu.edu/bladder/definitions.cfm]. Accessed on: 8 January 2014.</ref>
**Mostly useless in my experience.
*[[Urothelial carcinoma in situ]].
*[[Urothelial dysplasia]].


Invasion vs. in situ:
====Images====
Useful features - present in invasion:<ref>Sternberg, H4P, P.2047.</ref>
<gallery>
*Thin-walled vessels.
Image: Benign urothelium with large superficial cells -- intermed mag.jpg | Benign large superf. cells - intermed. mag. (WC)
*Stromal reaction (hypercellularity).
Image: Benign urothelium with large superficial cells -- high mag.jpg | Benign large superf. cells - high mag. (WC)
*Retraction artefact around the tumour cell nests.
Image: Benign urothelium with large superficial cells -- very high mag.jpg | Benign large superf. cells - very high mag. (WC)
</gallery>


====Staging====
===IHC===
*T1 - lamina propria.
*Ki-67 low.
**Several subdivisions of T1 exist:<ref>Sternberg, H4P 4th Ed., P.2048-9.</ref>
*p53 -ve.
***T1a - superficial or in muscularis mucosae.
***T1b - beyond muscularis mucosae - into submucosa.
*T2 - muscularis propria.


====Subtypes====
===Sign out===
There are numerous subtypes:<ref>URL: [http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html]. Accessed on: 19 August 2011.</ref>
<pre>
*Squamous differentiation.
URINARY BLADDER, TRANSURETHRAL BIOPSY:
*Clear cell.
- UROTHELIAL MUCOSA WITH MILD CHRONIC INFLAMMATION.
*Plasmacytoid.
- NO EVIDENCE OF MALIGNANCY.
*Micropapillary.
**Small nests (< ~10 cells/nest).
*Sarcomatoid.
*Many others...


=====Plasmacytoid urothelial cell carcinoma=====
COMMENT:
Features:
Levels were cut and show large benign umbrella cells.
*Abundant gray cytoplasm, eccentric nucleus.
</pre>


Images:
====Micro====
*[http://path.upmc.edu/cases/case267.html Plasmacytoid UCC - several images (upmc.edu)].
The sections show small fragments of urothelial mucosa with enlarged benign superficial epithelial cells. The lamina propria has a mild lymphocytic infiltrate. No papillary structures are identified. There is no significant nuclear atypia. Superficial small blood vessels appear congested.


===[[IHC]]===
==Urothelial dysplasia==
Features:
*[[AKA]] ''low-grade (urothelial) dysplasia''.
*CK7 +ve CK20 +ve.
{{Main|Urothelial dysplasia}}
**CK20 may be negative.


UCC vs. Prostate:
==Urothelial carcinoma in situ==
*UCC: p63+, PSA-, PSAP-, CK7+, CK20+.
*Abbreviated ''CIS''.
*Prostate: p63-, PSA+, PSAP+, CK7-, CK20-.
*[[AKA]] ''high-grade (urothelial) dysplasia''.
{{Main|Urothelial carcinoma in situ}}


UCC vs. RCC:
==Urothelial cell carcinoma==
*UCC: p63+.<ref>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Ratschek | first2 = M. | last3 = Tsybrovskyy | first3 = O. | last4 = Schips | first4 = L. | last5 = Zigeuner | first5 = R. | title = P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors. | journal = J Histochem Cytochem | volume = 51 | issue = 8 | pages = 1097-9 | month = Aug | year = 2003 | doi =  | PMID = 12871991 }}
:See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].
</ref>
*Abbreviated ''UCC''.
*[[AKA]] ''urothelial carcinoma''.
{{Main|Urothelial carcinoma}}


=Papillary urothelial lesions=
=Papillary urothelial lesions=
Line 236: Line 334:


==Urothelial papilloma==
==Urothelial papilloma==
===General===
{{Main|Urothelial papilloma}}
*Very rare diagnosed.
**If the person has a history of a low grade papillary urothelial carcinoma... it is a low grade papillary urothelial carcinoma.
**These cases are a consensus diagnosis, i.e. you show it to a colleague... if they agree you can call it.
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Papillary fronds.
*Minimal branching or fusion.
*Cytological features of normal urothelium.
**Normal urothelium approx. 2x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*No mitoses.


==Inverted urothelial papilloma==
==Inverted urothelial papilloma==
*[[AKA]] ''[[inverted papilloma]]''.
*[[AKA]] ''[[inverted papilloma]]''.
{{Main|Inverted urothelial papilloma}}
==Papillary urothelial neoplasm of low malignant potential==
*Abbreviated ''PUNLMP''.
**This is pronounced ''pun-lump''.
{{Main|Papillary urothelial neoplasm of low malignant potential}}
==Low-grade papillary urothelial carcinoma==
*Abbreviated ''LGPUC''.<ref name=pmid22857755>{{Cite journal  | last1 = Watts | first1 = KE. | last2 = Montironi | first2 = R. | last3 = Mazzucchelli | first3 = R. | last4 = van der Kwast | first4 = T. | last5 = Osunkoya | first5 = AO. | last6 = Stephenson | first6 = AJ. | last7 = Hansel | first7 = DE. | title = Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma. | journal = Urology | volume = 80 | issue = 2 | pages = 361-6 | month = Aug | year = 2012 | doi = 10.1016/j.urology.2012.04.010 | PMID = 22857755 }}</ref>
*[[AKA]] ''low-grade papillary urothelial cell carcinoma''.
{{Main|Low-grade papillary urothelial carcinoma}}
==High-grade papillary urothelial carcinoma==
*Abbreviated ''HGPUC''.
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
{{Main|High-grade papillary urothelial carcinoma}}
==Papillary urothelial hyperplasia==
*[[AKA]] ''papillary hyperplasia''.
*[[AKA]] ''reactive papillary hyperplasia''.
{{Main|Papillary urothelial hyperplasia}}
=Benign urothelial lesions=
===Cystitis===
*Inflammation of the [[urinary bladder]]. 
*Comes in many forms (see below).
*Typically a [[clinical diagnosis]] under the more general term [[urinary tract infection]].
Note:
*So called "[[giant cell cystitis]]" is dealt with separately; it is a benign non-pathologic change that may or may not be associated with inflammation.<ref name=Ref_Amin2_6>{{Ref Amin|2:6}}</ref>
===The big table of cystitis===
{| class="wikitable sortable"
! Type
! Key feature
! DDx
! Reference
|-
|Florid proliferative cystitis
| expanded lamina propria with [[von Brunn's nests]], [[cystitis cystica et glandularis]]
| [[von Brunn's nests]], [[cystitis cystica et glandularis]], low-grade urothelial carcinoma
| <ref name=Ref_GUP113>{{Ref GUP|113}}</ref>
|-
|[[Polypoid cystitis]]
| wide base, height > base
| papillary cystitis, bullous cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|Bullous cystitis
| wide base, height < base
| papillary cystitis, polypoid cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|Papillary cystitis
| narrow base, height > base
| polypoid cystitis, bullous cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|[[Interstitial cystitis]]
| +/-ulceration (uncommon) - requires clinical correlation
| urothelial CIS
| <ref name=Ref_GUP124>{{Ref GUP|124}}</ref>
|-
|Follicular cystitis
| lymphoid follicles
| non-Hodgkin [[lymphoma]]
| <ref name=Ref_GUP122>{{Ref GUP|122}}</ref>
|-
|Infectious cystitis
| dependent cause (bacterial, viral, fungal)
|
| <ref name=Ref_GUP127>{{Ref GUP|127}}</ref>
|-
|Granulomatous cystitis
| [[granuloma]]s
| [[tuberculosis]], [[schistosomiasis]], [[fungi|fungal infection]], post-BCG
| <ref name=Ref_GUP127>{{Ref GUP|127}}</ref>
|-
|Radiation cystitis
| edema, vascular congestion, +/- [[erosion]]s -- acute; fibrosis in LP and detrusor -- chronic
|
| <ref name=Ref_GUP138>{{Ref GUP|138}}</ref>
|}


===General===
==Interstitial cystitis==
*May be confused with papillary urothelial carcinoma with an inverted growth pattern.
{{Main|Interstitial cystitis}}


==Follicular cystitis==
===Microscopic===
===Microscopic===
Features:
Features:<ref name=Ref_GUP122>{{Ref GUP|122}}</ref>
*Like papillomas... but grow downward.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Lymphoid follicles in the lamina propria.
*According to THvdK,<ref>THvdK. 21 June 2010.</ref> ''inverted papillomas'' '''never''' have an exophytic component; if an exophytic component is present it is urothelial carcinoma.  This is disputed by one paper from Mexico that examines two cases.<ref name=pmid19433293>{{cite journal |author=Albores-Saavedra J, Chable-Montero F, Hernández-Rodríguez OX, Montante-Montes de Oca D, Angeles-Angeles A |title=Inverted urothelial papilloma of the urinary bladder with focal papillary pattern: a previously undescribed feature |journal=Ann Diagn Pathol |volume=13 |issue=3 |pages=158–61 |year=2009 |month=June |pmid=19433293 |doi=10.1016/j.anndiagpath.2009.02.009 |url=}}</ref>
*Nests have peripheral palisading of nuclei - '''important'''.


Images:
DDx:
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_high_mag.jpg Inverted papilloma - high mag. (WC)].
*Non-Hodgkin [[lymphoma]].
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_intermed_mag.jpg Inverted papilloma - intermed. mag. (WC)].


==Papillary urothelial neoplasm of low malignant potential==
===Sign out===
*Abbreviated ''PUNLMP''.
<pre>
URINARY BLADDER, BIOPSY:
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID NODULES WITH GERMINAL CENTRE FORMATION.
- MUSCULARIS PROPRIA PRESENT.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.
</pre>


==Polypoid cystitis==
===General===
===General===
*Uncommon: prevalence ~ 0-3.5%.<ref name=pmid19346063>{{cite journal |author=May M, Brookman-Amissah S, Roigas J, ''et al.'' |title=Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications |journal=Eur. Urol. |volume= 57|issue= 5|pages= 850|year=2009 |month=March |pmid=19346063 |doi=10.1016/j.eururo.2009.03.052 |url=}}</ref>
*Uncommon.
*PUNLMP vs. [[low grade papillary urothelial carcinoma]] has a poor inter-rater reliability.<ref name=pmid17095142>{{cite journal |author=MacLennan GT, Kirkali Z, Cheng L |title=Histologic grading of noninvasive papillary urothelial neoplasms |journal=Eur. Urol. |volume=51 |issue=4 |pages=889–97; discussion 897–8 |year=2007 |month=April |pmid=17095142 |doi=10.1016/j.eururo.2006.10.037 |url=}}</ref>
*Wide age range.
*Benign.


Treatment:
===Microscopic===
*Excision and on-going follow-up - like non-invasive [[low grade papillary urothelial carcinoma]].<ref name=pmid16697785>{{cite journal |author=Jones TD, Cheng L |title=Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts |journal=J. Urol. |volume=175 |issue=6 |pages=1995–2003 |year=2006 |month=June |pmid=16697785 |doi=10.1016/S0022-5347(06)00267-9 |url=}}</ref>
Features:<ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
*Polypoid urothelium-covered projections with:
*#Broad bases.
*#Height > base.
*#Extensive edema.


===Microscopic===
DDx:
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Papillary cystitis - not a broad base.
*Rare fused papillae.
*Bullous cystitis.
*Infrequent mitoses.
*Nuclei larger than papilloma - but monotonous.<ref name=Ref_GUP170>{{Ref GUP|170}}</ref>


Images:
Image:
*[http://en.wikipedia.org/wiki/File:Punlmp1.jpg PUNLMP - low mag. (WC)].
*[http://www.webpathology.com/image.asp?case=51&n=3 Polypoid cystitis (webpathology.com)].
*[http://en.wikipedia.org/wiki/File:Punlmp2.jpg PUNLMP - high mag. (WC)].


==Low grade papillary urothelial carcinoma==
==von Brunn nests==
*[[AKA]] ''low grade urothelial cell carcinoma''.
===General===
**Abbreviated ''low grade UCC''.
*Benign.


===Microscopic===
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
Features:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*Fused papillae.
*Nests of (benign) urothelium budding into the lamina propria.
*Papillae branch.
*Larger nuclei than PUNLMPs.


==High grade papillary urothelial carcinoma==
Note:
*[[AKA]] ''high grade urothelial cell carcinoma''.
*Nests should '''not''' extend into the muscularis propria.
**Abbreviated ''high grade UCC''.


===Microscopic===
DDx:
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*[[Nested urothelial cell carcinoma]].<ref name=pmid12960809>{{Cite journal  | last1 = Volmar | first1 = KE. | last2 = Chan | first2 = TY. | last3 = De Marzo | first3 = AM. | last4 = Epstein | first4 = JI. | title = Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. | journal = Am J Surg Pathol | volume = 27 | issue = 9 | pages = 1243-52 | month = Sep | year = 2003 | doi = | PMID = 12960809 }}</ref>
*"High grade nuclear features":
*[[Inverted urothelial papilloma|Inverted papilloma]].
**Nuclear pleomorphism - often 4-5x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*[[Cystitis cystica]] - have lumens, may be focal.
*Architectural complexity.
**Fused papillary common.
**Papillae branch.
*Mitoses common.


=Benign urothelial lesions=
===IHC===
==Brunn nests==
Features:<ref name=pmid12960809/>
Microscopic:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*p53 -ve.
*Benign inbudding nests of urothelium.
*MIB-1 <3%.
**Should lead to consideration of "inverted papilloma".


==Cystitis cystica==
==Cystitis cystica==
Microscopic:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
{{Main|Cystitis cystica}}
*Brunn nests with urothelium.


==Cystitis glandularis==
==Cystitis glandularis==
Microscopic:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
{{Main|Cystitis glandularis}}
*Brunn nests with cuboidal and columnar epithelium.


==Malakoplakia==
==Malakoplakia==
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==Nephrogenic adenoma==
==Nephrogenic adenoma==
*[[AKA]] ''mesonephric adenoma'',<ref name=pmid21716880>{{Cite journal  | last1 = Singh | first1 = KJ. | title = Mesonephric adenoma in remnant ureteric stump: A rare entity. | journal = Indian J Urol | volume = 27 | issue = 1 | pages = 140-1 | month = Jan | year = 2011 | doi = 10.4103/0970-1591.78414 | PMID = 21716880 }}</ref> [[AKA]] ''nephrogenic metaplasia''.
*[[AKA]] ''mesonephric adenoma''.
 
*[[AKA]] ''nephrogenic metaplasia''.
===General===
{{Main|Nephrogenic adenoma}}
Features:<ref name=pmid12118115>{{Cite journal  | last1 = Gokaslan | first1 = ST. | last2 = Krueger | first2 = JE. | last3 = Albores-Saavedra | first3 = J. | title = Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. | journal = Mod Pathol | volume = 15 | issue = 7 | pages = 765-70 | month = Jul | year = 2002 | doi = 10.1097/01.MP.0000019578.51568.24 | PMID = 12118115 | url = http://www.nature.com/modpathol/journal/v15/n7/full/3880603a.html }}</ref>
*Benign.
**May mimic adenocarcinoma!
*Classic location is the [[urinary bladder]].
**Also reported in ureter and prostatic urethra.
*It is thought to result from displacement of renal tubular cells, as this entity in renal transplant recipients is graft derived.<ref>{{Cite journal  | last1 = Mazal | first1 = PR. | last2 = Schaufler | first2 = R. | last3 = Altenhuber-Müller | first3 = R. | last4 = Haitel | first4 = A. | last5 = Watschinger | first5 = B. | last6 = Kratzik | first6 = C. | last7 = Krupitza | first7 = G. | last8 = Regele | first8 = H. | last9 = Meisl | first9 = FT. | title = Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients. | journal = N Engl J Med | volume = 347 | issue = 9 | pages = 653-9 | month = Aug | year = 2002 | doi = 10.1056/NEJMoa013413 | PMID = 12200552 }}</ref>
 
===Microscopic===
Features:<ref name=pmid12118115>{{Cite journal  | last1 = Gokaslan | first1 = ST. | last2 = Krueger | first2 = JE. | last3 = Albores-Saavedra | first3 = J. | title = Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. | journal = Mod Pathol | volume = 15 | issue = 7 | pages = 765-70 | month = Jul | year = 2002 | doi = 10.1097/01.MP.0000019578.51568.24 | PMID = 12118115 | url = http://www.nature.com/modpathol/journal/v15/n7/full/3880603a.html }}</ref>
*Tubular structures - '''key feature'''.
**Hobnailed cells.
**+/-Thick eosinophilic basement membrane.
**Microcystic appearance.
*Usu. assoc. with chronic inflammation.
 
Notes:
*May mimic vascular/lymphatic channels - can be sorted-out with IHC.
 
Images:
*www:
**[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-10-1455-f01&doi=10.1043%2F2010-0226-CR.1 NA (archivesofpathology.org)].<ref name=pmid20923300>{{Cite journal  | last1 = Kunju | first1 = LP. | title = Nephrogenic adenoma: report of a case and review of morphologic mimics. | journal = Arch Pathol Lab Med | volume = 134 | issue = 10 | pages = 1455-9 | month = Oct | year = 2010 | doi = 10.1043/2010-0226-CR.1 | PMID = 20923300 }}</ref>
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Nephrogenic_adenoma_-_intermed_mag.jpg Nephrogenic adenoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Nephrogenic_adenoma_-_very_high_mag.jpg Nephrogenic adenoma - very high mag. (WC)].


=See also=
=See also=
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{{reflist|2}}
{{reflist|2}}


[[Category:Uropathology]]
[[Category:Genitourinary pathology]]
Retrieved from "https://librepathology.org/wiki/Urothelium"